This is a first-in human, open-label, Phase 1 dose-escalation study in order to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for intravenous (IV) and/or subcutaneous (SC) dosing schemes of this combination treatment, and to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of this combination treatment in participants with relapsed/refractory B-cell non Hodgkin lymphoma (r/r NHL).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
53
RO7443904 will be administered by subcutaneous (SC) or IV infusion on Cycle (C) 1 Day (D) 10, C2D3, and C2D8. From C3 onward, RO7443904 will be given every 3 weeks (Q3W), for up to 12 cycles (C = 21 days).
Glofitamab will be administered through IV infusion starting with step-up dosing (2.5 mg/10 mg/30 mg) on C1D1, C1D8, and C2D1. Starting in Cycle 3, glofitamab will be given in 30 mg doses every three weeks (Q3W) with RO7443904, for up to 12 cycles (Cycle = 21 days).
Obinutuzumab will be administered once through IV infusion, at a 1 g dose in Cycle 1, on either Day -7, -4, or -3 (C1D-7, C1D-4, C1D-3).
Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).
MSKCC
New York, New York, United States
Cleveland Clinic Foundation; Hematology and Oncology
Cleveland, Ohio, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Peter MacCallum Cancer Centre; Department of Haematology
Melbourne, Victoria, Australia
Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT
København Ø, Denmark
CHRU Lille - Hôpital Claude Huriez; Service des Maladies du Sang
Lille, France
ASST PAPA GIOVANNI XXIII; Ematologia
Bergamo, Lombardy, Italy
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
Rozzano, Lombardy, Italy
Leicester Royal Infirmary; Dept of Haematology
Leicester, United Kingdom
Nature and frequency of dose-limiting toxicities (DLTs)
Time frame: From 3 weeks (21 days) from the first administration of RO7443904 (Cycle 2 Day 8) to 1 week after the second administration of RO7443904 (Cycle 3 Day 8)
Incidence, nature, and severity of AEs
graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and for cytokine-release syndrome (CRS) and neurotoxicity (immune effector cell-associated neurotoxicity syndrome; ICANS) according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Time frame: Up to 4 weeks after the last study treatment dose
Maximum concentration (Cmax) of RO7443904
Time frame: Up to 9 months
Area under the curve (AUC) of RO7443904
Time frame: Up to 9 months
Clearance (CL) of RO7443904
Time frame: Up to 9 months
Volume of distribution (Vd) of RO7443904
Time frame: Up to 9 months
Half-life (t1/2) of RO7443904
Time frame: Up to 9 months
Percentage of Participants with RO7443904 anti-drug antibodies (ADAs) during the study relative to the prevalence of ADA at baseline
Time frame: Up to 9 months
Time to maximum concentration (Tmax) of RO7443904
Time frame: Up to 9 months
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